4.5 Article

Hsa_circ_0000467 promotes cancer progression and serves as a diagnostic and prognostic biomarker for gastric cancer

期刊

出版社

WILEY
DOI: 10.1002/jcla.22726

关键词

biomarker; carcinogenesis; circular RNA; gastric cancer; hsa_circ_0000467

资金

  1. Construction Project of Fujian Province Minimally Invasive Medical Center [[2017]171]
  2. National Nature Science Foundation of China [81871899]
  3. second batch of special support funds for Fujian Province innovation and entrepreneurship talents [2016B013]
  4. QIHANG funds of Fujian Medical University [2016QH025]
  5. Scientific and technological innovation joint capital projects of Fujian Province [2016Y9031]

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Background Emerging evidence indicates that dysregulation of circular RNAs (circRNAs) is implicated in the development of malignancies. However, the diagnostic value and functional role of circRNAs in gastric cancer (GC) remain largely elusive. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to detect the expression of hsa_circ_0000467 in tissues, cell lines, and plasma. A receiver operating characteristic (ROC) curve was constructed to estimate the diagnostic value of hsa_circ_0000467. The association between the expression level of hsa_circ_0000467 and the clinicopathological features was analyzed. Moreover, cell functional assays were performed. Results Hsa_circ_0000467 was significantly upregulated in GC tissue compared to adjacent nontumor tissue (n = 51, P < 0.05). Similar results were detected in the HGC-27, MGC-803, AGS, NUGC-3, GES-1 cell lines (n = 15, P < 0.001), and in the plasma samples from GC patients (n = 20, P < 0.05). The area under the ROC curve of hsa_circ_0000467 was 0.790, which is superior to commonly used biomarkers including CEA and CA-724. We found that the expression levels of hsa_circ_0000467 in the same patient were significantly lower after surgery (n = 20, P < 0.05). Moreover, the hsa_circ_0000467 expression level is closely associated with TNM stage. Additionally, Cox multivariate analysis showed that hsa_circ_0000467 is a novel independent prognostic factor. Furthermore, in vitro experiments demonstrated that knockdown of hsa_circ_0000467 markedly inhibited the proliferation, migration, and invasion of GC cells. Moreover, hsa_circ_0000467 silencing increased tumor apoptosis in vitro. Conclusion Hsa_circ_0000467 can act as a novel noninvasive biomarker for the diagnosis and prognosis of GC and may be a potential therapeutic target for GC.

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